Chimeric Antigen Receptor-T Cell Therapy in Hematological Malignancies: Clinical Evidence and Challenges

Research efforts have focused on understanding and overcoming these barriers.Gumber and Wang [8] emphasize that CAR T cell exhaustion, driven by persistent antigen stimulation and an immunosuppressive microenvironment, reduces therapeutic potency.Strategies to mitigate exhaustion include modifications to CAR receptors and targeting pathways independent of CAR signaling.Similarly, Honikel and Olejniczak [9] discussed the importance of co-stimulatory receptor signaling in enhancing CAR-T cell function, suggesting that modulation of co-stimulatory signals can improve persistence and efficacy.Innovations in CAR-T cell engineering are also aimed at improving cell phenotype and reducing adverse effects.Zhu et al. [10] demonstrated that overexpressing RUNX3 in CAR-T cells maintains a less differentiated state, reduces CRS, and enhances resistance to exhaustion, thereby potentially improving safety and durability of responses.Furthermore, understanding the